title: The Impact of Model Uncertainty on Benchmark Dose Estimation.
abstract: We study the popular benchmark dose (BMD) approach for estimation of low exposure levels in toxicological risk assessment, focusing on dose-response experiments with quantal data. In such settings, representations of the risk are traditionally based on a specified, parametric, dose-response model. It is a well-known concern, however, that uncertainty can exist in specification and selection of the model. If the chosen parametric form is in fact misspecified, this can lead to inaccurate, and possibly unsafe, lowdose inferences. We study the effects of model selection and possible misspecification on the BMD, on its corresponding lower confidence limit (BMDL), and on the associated extra risks achieved at these values, via large-scale Monte Carlo simulation. It is seen that an uncomfortably high percentage of instances can occur where the true extra risk at the BMDL under a misspecified or incorrectly selected model can surpass the target BMR, exposing potential dangers of traditional strategies for model selection when calculating BMDs and BMDLs.
authors.affiliation: Department of Statistics, Texas A&M University, College Station, TX, USA.
authors.forename: R Webster
authors.initials: RW
authors.lastname: West
authors.forename: Walter W
authors.initials: WW
authors.lastname: Piegorsch
authors.forename: Edsel A
authors.initials: EA
authors.lastname: Peña
authors.forename: Lingling
authors.initials: L
authors.lastname: An
authors.forename: Wensong
authors.initials: W
authors.lastname: Wu
authors.forename: Alissa A
authors.initials: AA
authors.lastname: Wickens
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Wenhai
authors.initials: W
authors.lastname: Chen
keywords: AIC; BMDL; Benchmark analysis; Excess Risk; Extra; Model adequacy; Model selection; Quantitative risk assessment; Risk